The oral microbiome is a complex community that is intimately entwined with human health. Large-scale sequencing programs are beginning to reveal the vast species and genetic diversity of this community. However, efforts to characterize the oral microbiome on a functional level lag far behind. Recently, we have developed two new functional genomics technologies: chemical genetic profiling and Genetic Interaction Analysis Technology. I am interested in using these technologies to further a systems level understanding of the oral microbiome by investigating antibiotic action and cell envelope biology in E. coli. Antibiotic therapy has been shown to alter species balance in the human microbiome, and changes in this balance may be related to disease. Also, the human oral cavity has recently been suggested as a reservoir for the development of antibiotic resistance. Therefore, a comprehensive investigation of antibiotic action by chemical genetic profiling will provide valuable insights for informing future therapeutic efforts and managing the emergence of drug resistance. All antibiotics must interact with the cell envelope, as it is the compartment that protects the cell from its environment, presents antigens to the host, supports pathogenic secretion systems, and coordinates biofilm formation. Despite its clear medical importance, the envelope is poorly characterized. Genetic interaction analysis of the E. coli envelope will reveal new insights into the biology of this compartment. Given the conservation of function among bacteria, my findings will have implications for understanding antibiotic action and envelope function in the many gram-negative bacterial species of the human mouth and beyond. In addition, demonstrating the power of these gateway technologies will stimulate the development of comparable approaches in prevalent members of the oral microbiome.